Ornithine Technical Reports
Ornithine is an amino acid that works to prevent cancer and improve the
immune system. Here are a group of medical studies which describe this role for
Ornithine.
Here are a few definitions that may help:
| Polyamines |
Any compound containing two or more amine groups. |
| potent growth-inhibitory effect |
Something which stops cancer growth |
| ornithine decarboxylase |
Ornithine
Plus
Enzymes which can help the body remove carbon dioxide |
| ODC |
ornithine decarboxylase |
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Top
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Title |
Comments |
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...1... |
Transport of thyroid hormones to target tissues.
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...2... |
Biochemical and growth-modulatory effects of the new S-adenosylmethionine
decarboxylase inhibitor CGP 48664 in malignant and immortalized normal human breast
epithelial cells in culture. |
|
|
...3... |
Structure-activity relations of S-adenosylmethionine
decarboxylase inhibitors on the growth of MCF-7 breast cancer cells.
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...4... |
Polyamine profiles and growth properties of ornithine
decarboxylase overexpressing MCF-7 breast cancer cells in culture.
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...5... |
Prevention of breast cancer in premenopausal women.
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...6... |
Antiproliferative effect of curcumin (diferuloylmethane) against human
breast tumor cell lines. |
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...7... |
Can arginine and ornithine support gut
functions? |
"Dietary ornithine supplementation, in
the form of ornithine alpha-ketoglutarate (OKG) can be
considered as an arginine precursor. Several supplement studies have shown both amino
acids to promote growth hormone and insulin secretion with anabolic effects in
postoperative patients." |
|
...8... |
Chlorpheniramine inhibits the synthesis of ornithine
decarboxylase and the proliferation of human breast cancer cell lines [published erratum
appears in Breast Cancer Res Treat 1996;37(1):97]
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...9... |
Intrinsic and extrinsic factors in estrogen action in human breast cancer:
role of polyamines and pituitary factors. |
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..10... |
Ornithine alpha-ketoglutarate in nutritional
support. |
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..11... |
Role of ornithine decarboxylase in
proliferation of prolactin-dependent lymphoma cells.
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..12... |
Synthesis and biological evaluation of superactive agonists of growth
hormone-releasing hormone. |
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..13... |
Effects of parathyroid hormone-related peptide on adenosine
3',5'-monophosphate and ornithine decarboxylase in a human
colonic cell line. |
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..14... |
Effects of vasoactive intestinal peptide on adenosine 3',5'-monophosphate,
ornithine decarboxylase, and cell growth in a human colon
cell line. |
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..15... |
Characterization and growth factor stimulation of L-arginine transport in
a human colon cancer cell line. |
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..16... |
Epidermal growth factor labeled beta-amanitin-poly-L-ornithine:
preparation and evidence for specific cytotoxicity.
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...17... |
Role of polyamines in the growth of hormone-responsive and -resistant
human breast cancer cells in nude mice. |
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..18... |
Growth hormone testing for the diagnosis of growth hormone deficiency in
childhood: a population register-based study.
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...19... |
Insulin induction of ornithine decarboxylase.
Importance of mRNA secondary structure and phosphorylation of eucaryotic initiation
factors eIF-4B and eIF-4E. |
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..20... |
Polyamine involvement in the growth of hormone-responsive and -resistant
human breast cancer cells in culture. |
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Middle
Of The Menu |
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..21... |
Polyamine involvement in the secretion and action of TGF-alpha in hormone
sensitive human breast cancer cells in culture.
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..22... |
Failure of commercial oral amino acid supplements to increase serum growth
hormone concentrations in male body-builders.
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..23... |
Cellular and molecular basis of intestinal and pancreatic adaptation.
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..24... |
Effects of parathyroid hormone on ornithine
decarboxylase activity in human osteosarcoma cells.
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..25... |
Variations in amplification and expression of the ornithine
decarboxylase gene in human breast cancer cells.
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..26... |
Comparison of growth hormone response to growth hormone-releasing factor
1-44 according to the combined study of sleep secretion with the responses to
pharmacologic stimuli. |
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..27... |
Statistical study of 5473 results of nine pharmacological stimulation
tests: a proposed weighting index. |
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..28... |
Human promyelocytic cell line HL60 has the specific binding sites for
prolactin and its ornithine decarboxylase, DNA synthesis and
cellular proliferation are induced by prolactin.
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..29... |
Retinoic acid regulates ornithine
decarboxylase gene expression at the transcriptional level. |
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..30... |
Low-dose amino acid supplementation: no effects on serum human growth
hormone and insulin in male weightlifters.
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..31... |
Analogues of luteinizing hormone-releasing hormone containing cytotoxic
groups. |
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..32... |
Role of gastrin as a trophic hormone.
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..33... |
Regulation of rat ornithine decarboxylase
mRNA translation by its 5'-untranslated region.
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..34... |
Direct analysis of growth factor requirements for isolated human fetal
hepatocytes. |
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..35... |
Regulation of ornithine decarboxylase gene
expression in MCF-7 breast cancer cells by antiestrogens.
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..36... |
Involvement of the polyamine pathway in antiestrogen-induced growth
inhibition of human breast cancer. |
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..37... |
Intestinal adaptation in short-bowel syndrome.
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..38... |
Effects of estradiol on proliferation of endometrial adenocarcinoma cells
(Ishikawa line). |
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..39... |
Sensory deprivation stress and supplemental stimulation in the rat pup and
preterm human neonate. |
|
HealthGate Documents
Record 1 from database: MEDLINE
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- Title
- Transport of thyroid hormones to target tissues.
- Author
- Ekins RP; Sinha AK; Pickard MR; Evans IM; al Yatama F
- Address
- Division of Molecular Endocrinology, University College London Medical School, United
Kingdom.
- Source
- Acta Med Austriaca, 1994, 21:2, 26-34
- Abstract
- Endemic iodine deficiency is associated with maternal hypothyroxinemia and a relatively
high incidence of neurological disorders in the offspring. The previous assumption that
the placenta is impermeable to maternal thyroid hormone, has resulted in the erroneous
suggestion that iodine per se has an essential role in brain development. Furthermore, the
observed factorial rise in thyroxine-binding globulin (TBG) in pregnancy has often been
misinterpreted as preventing thyroid hormone loss to either the fetal compartment or
excretory systems. However, physiochemical analysis of the role of specific binding
proteins in hormone delivery, combined with epidemiological evidence and evolutionary
considerations has led us to postulate that a) maternal thyroxine (T4) is transported to
the fetus, and is of crucial importance in early fetal development, and b) TBG forms part
of a control system specifically designed to maintain at an optimal level the T4
environment to which the developing fetus is exposed. Placental transfer of maternal T4 in
a variety of mammalian species (including humans) is now well established. Further
experimental studies in rats have shown that perturbation of the intrauterine thyroid
hormone environment during critical phases of brain development results in a spectrum of
biochemical dysgenesis. For example, in fetal brains deriving from hypothyroxinemic (Tx)
rat dams, severe disruption of phosphate metabolism is observed and the ontogenesis of two
enzyme activities associated with growth control, protein kinase C and ornithine decarboxylase, are compromised. Development of brain
function is also impaired, as evidenced by the dysgenesis of certain neurotransmitter
metabolic activities (choline acetyltransferase and DOPA decarboxylase).(ABSTRACT
TRUNCATED AT 250 WORDS)
- Language of Publication
- English
- Unique Identifier
- 95091118
- MeSH Heading (Major)
- Fetal Development|*PH; Goiter, Endemic|*PP; Maternal-Fetal Exchange|*PH; Thyroid
Hormones|*BL
- MeSH Heading
- Animal; Brain|EM; Carrier Proteins|PH; Female; Fetal Organ Maturity|PH; Human; Infant,
Newborn; Membrane Proteins|PH; Pregnancy; Rats; Support, Non-U.S. Gov't; Thyroid Gland|EM;
Thyroxine|BL; Thyroxine-Binding Proteins|PH
- Publication Type
- JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL
- ISSN
- 0303-8173
- Country of Publication
- AUSTRIA
Record 2 from database: MEDLINE
Return To The Top
- Title
- Biochemical and growth-modulatory effects of the new S-adenosylmethionine decarboxylase
inhibitor CGP 48664 in malignant and immortalized normal human breast epithelial cells in
culture.
- Author
- Manni A; Badger B; Wechter R; Kunselman S; Rossini A; Demers L
- Address
- Department of Medicine, Pennsylvania State University College of Medicine, Hershey
17033, USA.
- Source
- Int J Cancer, 1995 Aug, 62:4, 485-91
- Abstract
- CGP 48664 [4-aminoindanon-1-(2'-amidino)hydrazone dihydrochloride monohydrate] is a
newly introduced inhibitor of S-adenosylmethionine decarboxylase (SAMDC) with increased
selectivity of action and reduced toxicity. We analyzed the biochemical and
antiproliferative effects of this compound in a panel of hormone-dependent (3 clones of
MCF-7, T47D) and -independent (MDA-MB-231, BT-20) human breast cancer cell lines in
culture. For comparison, we also tested its effects in the spontaneously immortalized
human breast epithelial cell line MCF-10A. All cell lines were highly sensitive to the
growth-inhibitor effect of CGP 48664 with an IC50 between 0.1 and 0.5 microM. A
dose-dependent bell-shaped increase in SAMDC was observed in normal and malignant breast
cells resulting from enzyme stabilization by the inhibitor as supported by Western blot
analysis. While ornithine decarboxylase (ODC) activity
consistently increased, the effect of CGP 48664 on spermidine/spermine N'acetyltransferase
(SSAT) was variable in the breast cancer cell lines. In contrast, the inhibitor
consistently reduced SSAT activity level in the MCF-10A cell line and its derivative
partially transformed by a mutated ras oncogene. As expected cellular putrescine levels
were markedly increased by CGP 48664 administration, whereas spermidine and spermine
contents were reduced. However, the degree of reduction was usually only moderate.
Furthermore, exogenous polyamine administration was relatively ineffective in rescuing the
antiproliferative effect of CGP 48664 in MCF-7 cells, while exerting a more complete
rescue in the MDA-MB-231 cell line. We conclude that CGP 48664 exerts a potent
growth-inhibitory effect on mammary cells in culture. However, its action may not always
be entirely mediated through the polyamine pathway.
- Language of Publication
- English
- Unique Identifier
- 95362369
- MeSH Heading (Major)
- Acetyltransferases|*ME; Adenosylmethionine Decarboxylase|*AI; Amidines|*PD;
Breast|*DE/EN/PA; Breast Neoplasms|*DT/EN/PA; Indans|*PD; Ornithine Decarboxylase|*ME
- MeSH Heading
- Cell Division|DE; Cell Line, Transformed; Dose-Response Relationship, Drug; Drug
Screening Assays, Antitumor; Human; Neoplasms, Hormone-Dependent|DT; Spermidine|ME/PD;
Spermine|PD; Support, U.S. Gov't, P.H.S.; Tumor Cells, Cultured
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0020-7136
- Country of Publication
- UNITED STATES
Record 3 from database: MEDLINE
Return To The Top
- Title
- Structure-activity relations of S-adenosylmethionine decarboxylase inhibitors on the
growth of MCF-7 breast cancer cells.
- Author
- Thomas T; Faaland CA; Adhikarakunnathu S; Thomas TJ
- Address
- Department of Environmental & Community Medicine, Environmental and Occupational
Health Sciences Institute, New Brunswick, NJ, USA.
- Source
- Breast Cancer Res Treat, 1996, 39:3, 293-306
- Abstract
- SAMDC is a key enzyme in the biosynthesis of spermidine and spermine, 2 polyamines that
are essential for cell proliferation. Inhibition of polyamine biosynthesis is often
targeted as a therapeutic strategy to suppress cancer cell growth as these cells contain
elevated levels of polyamines. We examined the effect of a new group of SAMDC inhibitors,
CGP33829, CGP35753, CGP36958, CGP39937, and CGP48664, (obtained from Ciba-Geigy, Basel,
Switzerland), and their parent compound, MGBG, on the proliferation of MCF-7 breast cancer
cells. MGBG had minimal effects on the proliferation of MCF-7 cells up to 6 microM
concentration. In contrast, CGP48664 and CGP39937, containing 2 aromatic rings that
delocalize the pi electron system of the backbone of MGBG, were potent inhibitors with 50%
growth inhibition at 0.5 microM concentration. Other CGP compounds were less effective in
inhibiting cell growth. The ability of CGP48664 to inhibit MCF-7 cell proliferation was
related to its ability to inhibit SAMDC and to consequently deplete spermidine and
spermine levels in the cell. Exogenous spermidine and spermine could reverse the growth
inhibitory effects of this compound. CGP compounds also increased the activity of ODC,
another enzyme involved in polyamine biosynthesis. Northern blot analysis of mRNA from
MCF-7 cells progressing in cell cycle after G1 synchronization did not show an increase in
ODC mRNA level by CGP48664. These data demonstrate structure-activity relationships of a
series of MGBG derivatives on cell growth, enzyme activities, and polyamine biosynthesis
in a hormone-responsive breast cancer cell line and suggest potential application of SAMDC
inhibitors as therapeutic agents.
- Language of Publication
- English
- Unique Identifier
- 97031083
- MeSH Heading (Major)
- Adenosylmethionine Decarboxylase|*AI/GE; Antineoplastic Agents|*PD; Breast
Neoplasms|*DT/PA; Enzyme Inhibitors|*PD
- MeSH Heading
- Acetyltransferases|ME; Amidines|PD; Biogenic Polyamines|AN; Cell Division|DE;
Estradiol|PD; Female; Human; Indans|PD; Mitoguazone|PD; Ornithine Decarboxylase|ME; RNA,
Messenger|AN; Structure-Activity Relationship; Support, U.S. Gov't, P.H.S.; Tumor Cells,
Cultured
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0167-6806
- Country of Publication
- NETHERLANDS
Record 4 from database: MEDLINE
Return To The Top
- Title
- Polyamine profiles and growth properties of ornithine
decarboxylase overexpressing MCF-7 breast cancer cells in culture.
- Author
- Manni A; Wechter R; Grove R; Wei L; Martel J; Demers L
- Address
- Department of Medicine, Pennsylvania State University College of Medicine, Hershey
17033, USA.
- Source
- Breast Cancer Res Treat, 1995 Apr, 34:1, 45-53
- Abstract
- To determine the direct influence of the polyamine (PA) pathway on breast cancer
phenotype, we employed a transfection approach to induce overexpression of the PA
biosynthetic enzyme ornithine decarboxylase (ODC) in the
hormone-responsive MCF-7 breast cancer cell line. Using a modified calcium phosphate
method and an ODC cDNA coding for a truncated and more stable enzyme, we were able to
achieve a moderate to marked degree of ODC overexpression (up to 150-fold) in a transient
transfection system. ODC-overexpressing MCF-7 cells exhibited a selective increase in
cellular putrescine content, while the levels of spermidine and spermine remained
unaffected. Under defined culture conditions, overexpression of ODC resulted in a
consistent but modest increase in [3H]thymidine incorporation into DNA which was similar
in the presence and absence of 17-beta-estradiol, TGF-alpha, and IGF-I. In the presence of
serum, the effect of ODC overexpression on basal [3H]-thymidine incorporation into DNA was
inconsistent, possibly as a result of subtle differences in culture conditions. Overall,
our results support the hypothesis that activation of the PA biosynthetic pathway may
confer a growth advantage to breast cancer cells.
- Language of Publication
- English
- Unique Identifier
- 95268110
- MeSH Heading (Major)
- Breast Neoplasms|*EN/GE/PA; Ornithine Decarboxylase|GE/*ME
- MeSH Heading
- Cell Division; Female; Gene Expression Regulation, Enzymologic; Human; Polyamines|ME;
Support, U.S. Gov't, P.H.S.; Transfection; Tumor Cells, Cultured
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0167-6806
- Country of Publication
- NETHERLANDS
Record 5 from database: MEDLINE
Return To The Top
- Title
- Prevention of breast cancer in premenopausal women.
- Author
- Love RR
- Address
- University of Wisconsin Comprehensive Cancer Center, Department of Human Oncology,
Madison 53706.
- Source
- J Natl Cancer Inst Monogr, 1994, :16, 61-5
- Abstract
- While all-inclusive complete models for breast cancer development are not available,
four concepts are likely to be critical to creation of well-grounded breast cancer
prevention efforts: 1) step-by-step progressive development, 2) involving multiple
factors, 3) over several years, and 4) during a long period of which the process may be
reversible. Interventions to prevent breast cancer must have a comprehensive biological
rationale, an absence of serious toxic effects, and long-term acceptability by women.
Prophylactic mastectomy may be beneficial in some women, but identification of individuals
at very high risk for breast cancer remains elusive. At present, greater attention to four
manipulable risk factors is appropriate: radiation, smoking, alcohol, and lactation.
Clinical trials are in the process of studying a synthetic retinoid
(4-hydroxyphenylretinamide), tamoxifen, and a low-fat diet. Other breast cancer prevention
strategies in various phases of preclinical trial evaluation include: pseudopregnancy, an
"ideal" combination oral contraceptive, luteinizing hormone-releasing hormone
(LHRH) agonist oophorectomy, modification of estrogen metabolism, suppression of ornithine decarboxylase induction, and manipulation of growth
factors.
- Language of Publication
- English
- Unique Identifier
- 95092435
- MeSH Heading (Major)
- Breast Neoplasms|EP/ET/*PC
- MeSH Heading
- Adult; Ataxia Telangiectasia|CO; Cocarcinogenesis; Contraceptives, Oral, Hormonal|AE/TU;
Dietary Fats|AD/AE; Estrogens|ME; Female; Fenretinide|PD; Gonadorelin|AG; Human;
Lactation; Mastectomy; Neoplasms, Radiation-Induced|PC; Ornithine Decarboxylase|AI;
Premenopause; Prospective Studies; Pseudopregnancy|CI; Randomized Controlled Trials; Risk
Factors; Smoking; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; Tamoxifen|TU;
Temperance; Time Factors
- Publication Type
- JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL
- ISSN
- 1052-6773
- Country of Publication
- UNITED STATES
Record 6 from database: MEDLINE
Return To The Top
- Title
- Antiproliferative effect of curcumin (diferuloylmethane) against human breast tumor cell
lines.
- Author
- Mehta K; Pantazis P; McQueen T; Aggarwal BB
- Address
- Department of Bioimmunotherapy, The University of Texas MD Anderson Cancer Center,
Houston 77030, USA.
- Source
- Anticancer Drugs, 1997 Jun, 8:5, 470-81
- Abstract
- Pharmacologically safe compounds that can inhibit the proliferation of tumor cells have
potential as anticancer agents. Curcumin, a diferuloylmethane, is a major active component
of the food flavor turmeric (Curcuma longa) that exhibits anticarcinogenic properties in
vivo. In vitro, it suppressed c-jun/Ap-1 and NF-kappaB activation and type 1 human
immunodeficiency virus long-terminal repeat-directed gene expression. We examined the
antiproliferative effects of curcumin against several breast tumor cell lines, including
hormone-dependent and -independent and multidrug-resistant (MDR) lines. Cell growth
inhibition was monitored by [3H]thymidine incorporation, Trypan blue exclusion, crystal
violet dye uptake and flow cytometry. All the cell lines tested, including the
MDR-positive ones, were highly sensitive to curcumin. The growth inhibitory effect of
curcumin was time- and dose-dependent, and correlated with its inhibition of ornithine decarboxylase activity. Curcumin preferentially arrested
cells in the G2/S phase of the cell cycle. Curcumin-induced cell death was neither due to
apoptosis nor to any significant change in the expression of apoptosis-related genes,
including Bcl-2, p53, cyclin B and transglutaminase. Overall our results suggest that
curcumin is a potent antiproliferative agent for breast tumor cells and may have potential
as an anticancer agent.
- Language of Publication
- English
- Unique Identifier
- 97358515
- MeSH Heading (Major)
- Antineoplastic Agents|*PD; Breast Neoplasms|*PA; Curcumin|*PD
- MeSH Heading
- Antibiotics, Anthracycline|PD; Blotting, Western; Cell Cycle|DE; Cell Division|DE; Cell
Line; Doxorubicin|PD; Drug Resistance, Multiple; Drug Resistance, Neoplasm; Drug Screening
Assays, Antitumor; Human; Ornithine Decarboxylase|ME; Support, Non-U.S. Gov't; Tetrazolium
Salts; Thiazoles
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0959-4973
- Country of Publication
- ENGLAND
Record 7 from database: MEDLINE
Return To The Top
- Title
- Can arginine and ornithine support gut functions?
- Author
- Cynober L
- Address
- Laboratoire de Biochimie, HÈopital Saint-Antoine, Paris, France.
- Source
- Gut, 1994 Jan, 35:1 Suppl, S42-5
- Abstract
- Arginine and ornithine are precursors of nitric oxide and
polyamines, respectively. These metabolites intimately participate in permeability and
adaptive responses of the gut. The liver possesses high arginase activity as an intrinsic
part of urea synthesis and would consume most of the portal supply of dietary arginine.
The gut reduces this possibility by converting dietary arginine to citrulline, which
effectively bypass the liver and is resynthesized to arginine in the kidney. Dietary ornithine supplementation, in the form of ornithine
alpha-ketoglutarate (OKG) can be considered as an arginine precursor. Several supplement
studies have shown both amino acids to promote growth hormone and insulin secretion with
anabolic effects in postoperative patients. Their intermediary metabolites (for example,
glutamine, proline) may also be of benefit in trauma metabolism. Specific effects of
either amino acid on the gut are poorly reported. One recent animal study showed improved
morphology after OKG administration, perhaps through increased polyamine secretion.
Generation of nitric oxide from arginine has two facets. Excess production from high dose
arginine potentiated the effects of experimentally induced sepsis, whereas low doses
improved survival. These considerations suggest that the role of enteral diet
supplementation with arginine or OKG should be urgently examined for any benefits it may
have on mucosal barrier function.
- Language of Publication
- English
- Unique Identifier
- 94171129
- MeSH Heading (Major)
- Arginine|*ME/PD; Enteral Nutrition|*; Intestines|DE/ME/*PH; Ornithine|*ME/PD
- MeSH Heading
- Citrulline|ME; Human; Nitric Oxide|ME
- Publication Type
- JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL
- ISSN
- 0017-5749
- Country of Publication
- ENGLAND
Record 8 from database: MEDLINE
Return To The Top
- Title
- Chlorpheniramine inhibits the synthesis of ornithine
decarboxylase and the proliferation of human breast cancer cell lines [published erratum
appears in Breast Cancer Res Treat 1996;37(1):97]
- Author
- Medina MA; García de Veas R; Morata P; Lozano J; Sánchez Jiménez F
- Address
- Laboratorio de BioquÆimica y BiologÆia Molecular, Facultad de Ciencias, Universidad de
MÆalaga, Spain.
- Source
- Breast Cancer Res Treat, 1995 Aug, 35:2, 187-94
- Abstract
- Proliferation of both mouse and human breast cancer cells was inhibited by
chlorpheniramine (CPA) in a dose-response manner. At the beginning of the exponential
phase of growth (two days after seeding), 250 microM CPA was able to reduce cell
proliferation by 75% (in Ehrlich cell cultures) and 30% (in MCF-7 cultures). The
antiproliferative effect of CPA was also tested on a poorly-differentiated and
hormone-insensitive human breast cancer cell line (MDA-MB231) and on a highly
proliferative human colon cancer cell line (clone 3). CPA was cytotoxic for MDA-MB231
cells at concentrations higher than 50 microM, and it was also cytotoxic for the colon
cancer cell clone 3 at 250 microM CPA. Nevertheless, colon cancer cells were slightly
stimulated at CPA concentrations less than 100 microM. CPA reduced (by 50-70%) the ornithine decarboxylase induction occurring early after culture
seeding of experimental mammary tumors (Ehrlich carcinoma cells) and human breast cancer
cells (MCF-7). The presented data suggest that in addition to ODC inhibition, CPA presents
other still unknown cytotoxic effects.
- Language of Publication
- English
- Unique Identifier
- 95375276
- MeSH Heading (Major)
- Breast Neoplasms|*EN/PA; Chlorpheniramine|*PD; Ornithine Decarboxylase|*BI/GE
- MeSH Heading
- Animal; Cell Division|DE; Colonic Neoplasms|EN/GE/PA; Dose-Response Relationship, Drug;
Gene Expression Regulation, Enzymologic|DE; Human; Mammary Neoplasms,
Experimental|EN/GE/PA; Mice; RNA, Messenger|GE; Support, Non-U.S. Gov't; Tumor Cells,
Cultured
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0167-6806
- Country of Publication
- NETHERLANDS
Record 9 from database: MEDLINE
Return To The Top
- Title
- Intrinsic and extrinsic factors in estrogen action in human breast cancer: role of
polyamines and pituitary factors.
- Author
- Shiu RP; Lima G; Leung CK; Dembinski TC
- Address
-
- Source
- J Steroid Biochem, 1986 Jan, 24:1, 133-8
- Abstract
- Although polyamines are important in regulating proliferation of mammalian cells, their
role in hormone induction of cell growth has not been delineated. In the
estradiol-responsive human breast cancer cell line, T-47D clone 11, estradiol (10(-10) M)
was able to stimulate cell proliferation and the activity of
- decarboxylase (ODC), the first and rate-limiting enzyme in the biosynthesis of
polyamines. alpha-Difluoromethylornithine (DFMO), a specific inhibitor of ODC, blocked the
estradiol-induced cell proliferation and ODC activity. Exogenous addition of putrescine,
the natural product of ODC, rescued the inhibitory effect of DFMO. In addition, DFMO
abolished the estradiol-induced growth of several other estrogen-responsive human breast
cancer cell lines but did not affect the growth of hormone-independent cell lines.
Further, a serum factor was found to be required for estradiol to exert its effect. To
gain insight into the nature of this and possibly other extrinsic factors involved, the
effect of estradiol on the proliferation of T-47D cells transplanted into athymic nude
mouse was evaluated. In this in vivo system, estradiol alone produced only moderate growth
of the human breast tumor. The simultaneous transplantation of a prolactin (PRL)- and
growth hormone (GH)-secreting rat pituitary tumor or normal rat pituitary glands at a
different site dramatically potentiated the effect of estradiol on the growth of the
breast tumor xenograft. Purified PRL or GH were without effect, indicating that the active
pituitary factor is neither PRL nor GH. Further, conditioned medium from rat pituitary
tumor cells potentiated the mitogenic effect of estradiol on T-47D and several other
estrogen receptor-positive human breast cancer cell lines in vitro under serum-free
condition. In conclusion, we have identified both intrinsic (polyamines) and extrinsic
(pituitary/serum) factors that are importance for estrogen to exert its mitogenic action.
The next goal will be to elucidate the mechanisms of action of these molecules in the
modulation of estrogen action.
- Language of Publication
- English
- Unique Identifier
- 86201682
- MeSH Heading (Major)
- Breast Neoplasms|*PA; Estrogens|*PD; Pituitary Gland|*PH; Polyamines|*ME
- MeSH Heading
- Animal; Cell Line; Drug Synergism; Female; Human; Mice; Mice, Nude; Neoplasm
Transplantation; Ornithine|AA/PD; Ornithine Decarboxylase|AN; Pituitary Neoplasms|SE;
Support, Non-U.S. Gov't; Transplantation, Heterologous
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0022-4731
- Country of Publication
- ENGLAND
- CAS Registry/EC Number
- EC 4.1.1.17 (Ornithine Decarboxylase); 0 (Estrogens); 0 (Polyamines); 70052-12-9
(Eflornithine); 7006-33-9 (Ornithine)
Record 10 from database: MEDLINE
Return To The Top
- Title
- Ornithine alpha-ketoglutarate in nutritional support.
- Author
- Cynober L
- Address
- Laboratoire de Biochimie, Hopital Saint Antoine, Paris, France.
- Source
- Nutrition, 1991 Sep-Oct, 7:5, 313-22
- Abstract
- Ornithine alpha-ketoglutarate (OKG) is a salt formed of two
molecules of ornithine and one molecule of
alpha-ketoglutarate. OKG has been successfully used by the enteral and parenteral route in
burn, traumatized, and surgical patients and in chronically malnourished subjects.
According to the metabolic situation, OKG treatment decreases muscle protein catabolism
and/or increases synthesis. In addition, OKG promotes wound healing. The mechanism of
action of OKG is not fully understood, but the secretion of anabolic hormones (insulin,
human growth hormone) and the synthesis of metabolites (glutamine, polyamines, arginine,
ketoacids) may be involved.
- Language of Publication
- English
- Unique Identifier
- 92208515
- MeSH Heading (Major)
- Nutrition|*; Ornithine|*AA/AD/AE/CH/ME/PK/TU
- MeSH Heading
- Animal; Chemistry, Physical; Enteral Nutrition; Human; Nutrition Disorders|TH;
Parenteral Nutrition; Wound Healing
- Publication Type
- JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL
- ISSN
- 0899-9007
- Country of Publication
- UNITED STATES
- CAS Registry/EC Number
- 37339-58-5 (ornicetil); 7006-33-9 (Ornithine)
Record 11 from database: MEDLINE
Return To The Top
- Title
- Role of ornithine decarboxylase in proliferation of
prolactin-dependent lymphoma cells.
- Author
- Elsholtz HP; Shiu RP; Friesen HG
- Address
-
- Source
- Biochem Cell Biol, 1986 May, 64:5, 381-6
- Abstract
- Mitogenic stimulation of Nb2 lymphoma cells by lactogenic hormones (prolactin, human
growth hormone) caused a dramatic early increase in ornithine
decarboxylase (ODC) activity that achieved a maximal level by 6-8 h. A marked increase in
ODC activity was also generated when cells which had reached a growth plateau were
transferred to fresh medium that did not stimulate growth. Furthermore, low concentrations
of human growth hormone (20 pg/mL) elicited a proliferative response, but did not cause a
detectable early increase in ODC activity. The early peak of ODC activity thus appeared
not to be directly involved in mediating lactogen-stimulated growth nor was it required to
support the mitogenic response. However, prolonged suppression of ODC activity by
DL-alpha-difluoromethylornithine (DFMO) (200 microM) attenuated the growth of Nb2 cells
(50-60% inhibition), indicating that normal cell growth was dependent on ODC and polyamine
biosynthesis. Under these conditions, putrescine, the enzyme product, or the polyamines
spermidine and spermine restored normal cell growth when added at a concentration of 1
microM or greater. Nb2-SP cells, variants which proliferate in the absence of prolactin,
were about two times more resistant to the growth suppressive effects of DFMO than
prolactin-responsive Nb2 cells.
- Language of Publication
- English
- Unique Identifier
- 86242765
- MeSH Heading (Major)
- Lymphoma|EN/*PA; Ornithine Decarboxylase|AI/*ME; Prolactin|*PD; Somatotropin|*PD
- MeSH Heading
- Animal; Cell Division|DE; Cell Line; Human; Kinetics; Ornithine|AA/PD; Support, Non-U.S.
Gov't
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0829-8211
- Country of Publication
- CANADA
- CAS Registry/EC Number
- EC 4.1.1.17 (Ornithine Decarboxylase); 70052-12-9 (Eflornithine); 7006-33-9 (Ornithine);
9002-62-4 (Prolactin); 9002-72-6 (Somatotropin)
Record 12 from database: MEDLINE
Return To The Top
- Title
- Synthesis and biological evaluation of superactive agonists of growth hormone-releasing
hormone.
- Author
- Izdebski J; Pinski J; Horvath JE; Halmos G; Groot K; Schally AV
- Address
- Department of Medicine, Tulane University School of Medicine, New Orleans, LA 70146,
USA.
- Source
- Proc Natl Acad Sci U S A, 1995 May, 92:11, 4872-6
- Abstract
- Analogs of the 29 amino acid sequence of human growth hormone-releasing hormone (hGH-RH)
with agmatine (Agm) in position 29, desaminotyrosine (Dat) in position 1, norleucine (Nle)
in position 27, and L-alpha-aminobutyric acid (Abu) in position 15 have been synthesized,
and their biological activity was evaluated. Some peptides contained one or two residues
of ornithine (Orn) instead of Lys in positions 12 and 21 and
additional replacements in positions 8 and 28. All analogs were found to be more potent
than hGH-RH-(1-29)-NH2 in the superfused rat pituitary cell system. In tests in vivo in
rats after subcutaneous administration, the analogs JI-22, [Dat1, Orn12,21, Abu15, Nle27,
Agm29]hGH-RH-(1-29); JI-34, [Dat1, Orn12,21,Abu15,Nle27, Asp28, Agm29]hGH-RH-(1-29);
JI-36, [Dat1, Thr8, Orn12,21, Abu15,Nle27,Asp28,Agm29]hGH-RH-(1-29); and JI-38,
[Dat1,Gln8, Orn12,21,Abu15,Nle27,Asp28,Agm29]hGH-RH-(1 -29) displayed a potency
44.6,80.9,95.8, and 71.4 times greater, respectively, than that of hGH-RH-(1-29)-NH2 at 15
min and 217.1, 89.7, 87.9, and 116.8 times greater at 30 min. After intravenous
administration, JI-22, JI-36, and JI-38 were 3.2-3.8 times more potent than
hGH-RH-(1-29)-NH2 at 5 min and 6.1-8.5 times more active at 15 min. All analogs were found
to have higher binding affinities for GH-RH receptors on rat pituitary cells than
hGH-RH-(1-29)-NH2. Because of high activity and greater stability, these analogs could be
considered for therapy of patients with growth hormone deficiency.
- Language of Publication
- English
- Unique Identifier
- 95281558
- MeSH Heading (Major)
- Oligopeptides|CS/*PD; Pituitary Gland|DE/*SE; Somatotropin|BL/*SE;
Somatotropin-Releasing Hormone|*AA/AG/*CS/PD
- MeSH Heading
- Amino Acid Sequence; Animal; Comparative Study; Human; In Vitro; Male; Molecular
Sequence Data; Rats; Rats, Sprague-Dawley; Receptors, Neuropeptide|ME; Receptors,
Pituitary Hormone-Regulating Hormone|ME; Structure-Activity Relationship; Support, U.S.
Gov't, Non-P.H.S.
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0027-8424
- Country of Publication
- UNITED STATES
Record 13 from database: MEDLINE
Return To The Top
- Title
- Effects of parathyroid hormone-related peptide on adenosine 3',5'-monophosphate and ornithine decarboxylase in a human colonic cell line.
- Author
- Yu D; Seitz PK; Selvanayagam P; Rajaraman S; Townsend CM Jr; Cooper CW
- Address
- Department of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston
77550.
- Source
- Endocrinology, 1992 Apr, 130:4, 1993-2000
- Abstract
- PTH-related peptide (PTHrP) is widely distributed in normal tissues, including the gut,
and is considered a potential autocrine or paracrine regulator of cellular growth and
differentiation. With this in mind, a human colonic cell line (LoVo) was used to study the
effect of PTHrP on ornithine decarboxylase (ODC), because ODC
is known to have profound effects on the growth and differentiation of many cell types via
stimulation of synthesis of polyamines. cAMP also was measured, because this second
messenger has been implicated in the regulation of ODC activity. Nearly confluent LoVo
cells, grown in F-12 medium and 10% fetal bovine serum (FBS), were preincubated in 1% FBS
for at least 5 h, and then PTHrP-(1-34) was added, and the incubation was continued for up
to 6 h. Cell extracts were analyzed for ODC activity by measuring 14CO2 liberated from
14C-labeled ornithine, for cAMP by RIA, and for ODC mRNA by
Northern analysis. PTHrP produced dose-related increases in both cAMP (2- to 3-fold) and
ODC (3- to 5-fold), with a maximal effect at 0.1-1 microM and an ED50 of 1-10 nM.
Comparison of the cAMP and ODC responses to PTHrP showed a strong correlation (r = 0.96; P
less than 0.001). The effects of 1 microM PTHrP-(1-34) to increase cAMP and ODC were
completely inhibited by 10-20 microM of the specific antagonist [Asn10,Leu11]PTHrP-(7-34).
PTHrP-(1-34) did not stimulate ODC activity when cells were incubated without FBS. The
stimulation of ODC activity by PTHrP-(1-34) was maximal at 2 h, a time at which an
increase in ODC mRNA also was evident. PTH-(1-34) and forskolin also stimulated ODC
activity, but PTHrP-(67-86) amide was ineffective. The results indicate that the
N-terminal portion of the PTHrP molecule can stimulate ODC activity in a human colon cell
line and that the effect is probably mediated by cAMP. The results are consistent with the
idea that PTHrP may influence cell growth and differentiation in the gut via an effect on
polyamine biosynthesis. Since LoVo cells also express PTHrP mRNA, this gastrointestinal
cell line may serve as a useful model for studying autocrine regulation of gut cell growth
and differentiation by PTHrP.
- Language of Publication
- English
- Unique Identifier
- 92191895
- MeSH Heading (Major)
- Colon|CH/*DE; Cyclic AMP|*AN; Ornithine Decarboxylase|*AN/GE; Parathyroid Hormones|*PD;
Proteins|GE/*PD
- MeSH Heading
- Cell Line; Human; Peptide Fragments|PD; RNA, Messenger|AN; Support, U.S. Gov't, P.H.S.
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0013-7227
- Country of Publication
- UNITED STATES
- CAS Registry/EC Number
- EC 4.1.1.17 (Ornithine Decarboxylase); 0 (parathyroid hormone-related protein); 0
(Parathyroid Hormones); 0 (Peptide Fragments); 0 (Proteins); 0 (RNA, Messenger);
112540-82-6 (hypercalcemic hormone of malignancy (1-34)); 52232-67-4 (Teriparatide);
60-92-4 (Cyclic AMP)
Record 14 from database: MEDLINE
Return To The Top
- Title
- Effects of vasoactive intestinal peptide on adenosine 3',5'-monophosphate, ornithine decarboxylase, and cell growth in a human colon cell
line.
- Author
- Yu D; Seitz PK; Selvanayagam P; Rajaraman S; Townsend CM Jr; Cooper CW
- Address
- Department of Pharmacology, University of Texas Medical Branch, Galveston 77550.
- Source
- Endocrinology, 1992 Sep, 131:3, 1188-94
- Abstract
- Vasoactive intestinal peptide (VIP) is a widely distributed neuropeptide that has been
considered a potential regulator of cell growth and differentiation in various tissues,
including the gut. To examine this idea, we used a human colon carcinoma cell line (LoVo)
as a model system and measured ornithine decarboxylase (ODC),
because this is the rate-limiting enzyme for the formation of polyamines, which are
thought to be key factors in regulating cell growth. LoVo cells, grown to about 80%
confluence in F-12 medium containing 10% fetal bovine serum, were preincubated for 5 h in
low serum medium (1% fetal bovine serum in F-12), and ODC activity was determined by
measuring 14CO2 liberated from 14C-labeled ornithine. VIP
caused a dose-related biphasic change in ODC, with activity increased at 10 pM, maximal
(5-fold increase) at 10 nM, and decreased toward basal at 100 nM to 1 microM. Incubation
of cells for 6 days with VIP in low serum medium showed similar changes in cell numbers,
with growth being increased by doses in the 1 pM to 100 nM range and decreased at higher
doses (greater than or equal to 100 nM). Exposure of cells to 5 mM alpha-difluoromethylornithine blocked both the VIP-induced increase in cell number and
the VIP-induced increase in ODC activity. Increased ODC mRNA was detected after 2 h of
exposure to VIP, a time at which ODC activity peaked after treatment, and the increase in
ODC mRNA caused by VIP was dose-dependent. In related experiments LoVo cells were found to
have high affinity VIP receptors (Kd = 0.4 nM), as assessed by examination of [125I]VIP
binding in the presence of varying concentrations of unlabeled VIP. Studies of
intracellular cAMP revealed a dose-related increase in cAMP in response to VIP (ED50 = 11
pM), and the adenylate cyclase activator forskolin increased both ODC activity and ODC
mRNA. The findings support the idea that LoVo cells have VIP receptors linked to cAMP
which can stimulate cell growth at least in part by increasing ODC synthesis and activity,
thereby altering the production of polyamines. The decreased growth and ODC activity
observed with high doses of VIP may involve a second messenger other than cAMP.
- Language of Publication
- English
- Unique Identifier
- 92371314
- MeSH Heading (Major)
- Cell Division|*DE; Cyclic AMP|*ME; Ornithine Decarboxylase|GE/*ME; Vasoactive Intestinal
Peptide|ME/*PD
- MeSH Heading
- Adenocarcinoma; Blotting, Northern; Cell Line; Colonic Neoplasms; Dose-Response
Relationship, Drug; Eflornithine|PD; Human; Kinetics; Receptors, Gastrointestinal
Hormone|ME; RNA, Messenger|ME; RNA, Neoplasm|GE/IP; Support, U.S. Gov't, P.H.S.
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0013-7227
- Country of Publication
- UNITED STATES
- CAS Registry/EC Number
- EC 4.1.1.17 (Ornithine Decarboxylase); 0 (Receptors, Gastrointestinal Hormone); 0
(Receptors, Vasoactive Intestinal Peptide); 0 (RNA, Messenger); 0 (RNA, Neoplasm);
37221-79-7 (Vasoactive Intestinal Peptide); 60-92-4 (Cyclic AMP); 70052-12-9
(Eflornithine)
Record 15 from database: MEDLINE
Return To The Top
- Title
- Characterization and growth factor stimulation of L-arginine transport in a human colon
cancer cell line.
- Author
- Cendan JC; Souba WW; Copeland EM 3rd; Lind DS
- Address
- Department of General Surgery, University of Florida College of Medicine, Gainesville
32610, USA.
- Source
- Ann Surg Oncol, 1995 May, 2:3, 257-65
- Abstract
- BACKGROUND: Epidermal growth factor (EGF) and transforming growth factor alpha (TGF
alpha) are potent mitogens that contribute to abnormal growth regulation in colon cancer.
Growth factors have been shown to regulate transmembrane nutrient uptake as an adaptive
response to support cellular proliferation. METHODS: The transport of L-arginine by the
SW480 primary human colon adenocarcinoma cell line was characterized by assaying the
uptake of [3H]L-arginine in the presence and absence of sodium. Kinetic studies were
performed over a range of L-arginine concentrations to determine transport affinity (Km)
and maximal transport velocity (Vmax). To further characterize the specific transporters,
[3H]L-arginine uptake was measured in the presence of selected amino acids, hormones, and
under conditions of varying external pH. To investigate the effects of EGF and TGF alpha,
cells were incubated with increasing doses of growth factors (1, 10, 50 ng/ml) and
L-arginine transport was measured at various time intervals (8, 12, 24 h). Proliferation
was assessed by the colorimetric 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium
bromide (MTT) assay 3 days after growth factor stimulation. RESULTS: The majority of
carrier-mediated L-arginine transport was via a sodium-independent process (65-70%),
whereas the remainder was sodium-dependent (28-30%). Diffusion contributed a small amount
to total L-arginine uptake (2%). Kinetic studies of arginine transport revealed a single
high-affinity Na(+)-independent transporter with a Km = 55.8 +/- 5.8 microM and a Vmax =
710.6 +/- 87.3 pM/mg protein/30 s. Na(+)-independent arginine uptake was pH-insensitive
and markedly inhibited by system y+ substrates L-homoarginine, L-lysine, and L-ornithine. A single Na(+)-dependent transporter with a Km = 19.8
+/- 2.3 microM and a Vmax = 159.1 +/- 8.9 pM/mg protein/30 s was identified.
Na(+)-dependent arginine uptake was inhibited by system BO,+ substrates L-lysine, L-ornithine, L-leucine, L-cysteine, and L-glutamine, but not by
2-methylaminoisobutyric acid. In addition, Na(+)-dependent arginine uptake was pH- and
hormone-insensitive. Incubation with EGF or TGF alpha had no effect on Na(+)-independent
L-arginine uptake; however, Na(+)-dependent uptake was enhanced 60% by EGF (10 ng/ml, p
< 0.05) and 100% by TGF alpha (10 ng/ml, p < 0.05), whereas cellular proliferation
was increased 27% by EGF (10 ng/ml, p < 0.05) and 37% by TGF alpha (10 ng/ml, p <
0.01). CONCLUSIONS: L-arginine transport in the SW480 colon cancer cell line is
principally mediated by the Na(+)-independent system y+ and to a lesser extent by the
Na(+)-dependent system BO,+. Furthermore, EGF and TGF alpha preferentially stimulate
L-arginine uptake via the Na(+)-dependent transporter, ostensibly to accommodate for the
mitogenic stimulus.
- Language of Publication
- English
- Unique Identifier
- 95368445
- MeSH Heading (Major)
- Adenocarcinoma|*ME; Arginine|*PK; Colonic Neoplasms|*ME; Epidermal Growth
Factor-Urogastrone|CH/*PD; Transforming Growth Factor alpha|CH/*PD
- MeSH Heading
- Amino Acids|PD; Carrier Proteins; Cell Division|DE; Cell Membrane Permeability|DE;
Human; Hydrogen-Ion Concentration; Ion Channel Gating|DE; Nitric Oxide|BI; Radioisotopes;
Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; Time Factors; Tumor Cells,
Cultured|ME
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 1068-9265
- Country of Publication
- UNITED STATES
Record 16 from database: MEDLINE
Return To The Top
- Title
- Epidermal growth factor labeled beta-amanitin-poly-L-ornithine:
preparation and evidence for specific cytotoxicity.
- Author
- Bermbach U; Faulstich H
- Address
- Max-Planck-Institut für medizinische Forschung, Abteilung Physiologie, Heidelberg, West
Germany.
- Source
- Biochemistry, 1990 Jul 24, 29:29, 6839-45
- Abstract
- Poly-L-ornithine with an average molecular weight of 32K was reacted with beta-amanitin
hydroxysuccinimide ester to form an amide-linked toxin conjugate. Loading of the polymeric
chain with amanitin was high, corresponding to up to 35% of the total weight. To this
amatoxin vehicle we attached a targeting molecule, human recombinant leucine-21 epidermal
growth factor (hrEGFL), via a disulfide-containing linker moiety. A typical average
stoichiometry of the hrEGFL labeled toxin conjugate was
(L-Orn)164(beta-amanitin)19(COC2H4SSC2H4CO-hrEGFL)2. The affinity for EGF receptors of
hrEGFL bound in this conjugate was tested by using A 431 cells. The affinity was eight
times lower than that of unsubstituted hrEGFL but regarded as high enough for studying
specific toxicity effects with cells bearing EGF receptors. We found that beta-amanitin in
the labeled conjugate was able to inhibit the growth of A 431 cells at a concentration of
28 nM, 80 times lower than for native beta-amanitin and 20 times lower than for poly-L-ornithine-bound beta-amanitin without the hrEGFL label. The
approximately 20-fold enhancement of cytotoxicity suggests a specific internalization of
the toxin conjugate mediated by the hormone label. This idea is supported by the fact that
also in another transformed fibroblast cell line, with an increased though smaller number
of EGF receptors than A 431 cells, the corresponding enhancement of cytotoxicity was
demonstrable but less pronounced (7-fold). The hormone-mediated increase in cytotoxicity
of EGF labeled poly-L-ornithine-beta-amanitin conjugates,
combined with their moderate toxicity in the mouse, encourages further examination of such
compounds in tumor model systems in vivo.(ABSTRACT TRUNCATED AT 250 WORDS)
- Language of Publication
- English
- Unique Identifier
- 90373797
- MeSH Heading (Major)
- Amanitins|*/TO; Epidermal Growth Factor-Urogastrone|*/ME; Peptides|*
- MeSH Heading
- Animal; Cytotoxins; Human; Receptors, Epidermal Growth Factor-Urogastrone|ME; Support,
Non-U.S. Gov't; Tumor Cells, Cultured|DE/ME
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0006-2960
- Country of Publication
- UNITED STATES
- CAS Registry/EC Number
- 0 (Amanitins); 0 (Cytotoxins); 0 (Peptides); 0 (Receptors, Epidermal Growth
Factor-Urogastrone); 21150-22-1 (beta-amanitin); 25104-12-5 (polyornithine); 62229-50-9
(Epidermal Growth Factor-Urogastrone)
Record 17 from database: MEDLINE
Return To The Top
- Title
- Role of polyamines in the growth of hormone-responsive and -resistant human breast
cancer cells in nude mice.
- Author
- Manni A; Badger B; Martel J; Demers L
- Address
- Department of Medicine, Pennsylvania State University, Hershey 17033.
- Source
- Cancer Lett, 1992 Sep 14, 66:1, 1-9
- Abstract
- Recent in vitro data suggest that at least some hormone-independent breast cancer cells
exhibit increased polyamine biosynthesis and resistance to antipolyamine therapy. To
address this issue under conditions of in vivo growth, we tested the antiproliferative
effect of the polyamine synthetic inhibitor alpha-difluoromethyl-ornithine
(DFMO) on hormone-dependent (MCF-7) and -independent (MDA-MB-231, BT-20) breast cancer
cell lines growing in nude mice. We observed that DFMO significantly inhibited the growth
of established tumors to a similar extent in all cell lines, even though tumor regression
was only observed with MCF-7 cells. DFMO, while inhibiting E2-supported MCF-7 breast
cancer growth, did not inhibit E2-stimulated progesterone receptor synthesis. Cellular
levels of polyamines were highest in MCF-7 cells and lowest in the BT-20 cell line. Tumor
content of spermidine was similarly suppressed by DFMO treatment in the 3 cell lines,
while the spermine level was unaffected. Cellular putrescine levels were suppressed in
MCF-7 and BT-20 cells. Administration of DFMO prior to implantation of fragments of MCF-7
or MDA-MB-231 tumors in nude mice significantly inhibited tumor development to a similar
extent. The action of DFMO seemed to be predominantly tumoristatic since new tumors
develop in some mice upon discontinuation of the drug. We conclude that the
hormone-independent breast cancer cell lines tested do not exhibit increased polyamine
biosynthesis or resistance to antipolyamine therapy when grown in vivo in nude mice.
- Language of Publication
- English
- Unique Identifier
- 93082651
- MeSH Heading (Major)
- Breast Neoplasms|DT/*PA/PP; Neoplasms, Hormone-Dependent|DT/*PA/PP; Polyamines|*
- MeSH Heading
- Animal; Cell Division|DE; Comparative Study; Drug Resistance; Drug Screening Assays,
Antitumor; Eflornithine|PD; Human; Mice; Mice, Nude; Neoplasm Transplantation;
Putrescine|ME/PH; Spermidine|ME/PH; Spermine|ME/PH; Support, U.S. Gov't, P.H.S.; Tumor
Cells, Cultured|DE
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0304-3835
- Country of Publication
- NETHERLANDS
- CAS Registry/EC Number
- 0 (Polyamines); 110-60-1 (Putrescine); 124-20-9 (Spermidine); 70052-12-9 (Eflornithine);
71-44-3 (Spermine)
Record 18 from database: MEDLINE
Return To The Top
- Title
- Growth hormone testing for the diagnosis of growth hormone deficiency in childhood: a
population register-based study.
- Author
- Carel JC; Tresca JP; Letrait M; Chaussain JL; Lebouc Y; Job JC; Coste J
- Address
- Association France Hypophyse, HÈopital Cochin, Paris, France. jccarel@infobiogen.fr
- Source
- J Clin Endocrinol Metab, 1997 Jul, 82:7, 2117-21
- Abstract
- Evaluation of GH secretion using pharmacological GH stimulation tests (GHST) remains a
current practice, although the reliability of GHST has been questioned, and many pitfalls
have been pointed out. We have analyzed all of the 6373 GH stimulation tests that led to
the initiation of GH therapy in 3233 children treated in France from 1973-1989. Tests and
GH measurements were performed by individual centers and collected by the Association
France-Hypophyse. GH deficiency (GHD) was due to craniospinal irradiation (11%), was due
to organic causes or associated with multiple deficiencies (22%), or was considered
idiopathic (65%); 2% of the patients were considered non-GHD. Eleven different
pharmacological tests were used, and 62 of the 66 theoretical pairs of tests were used at
least once. The most frequent combination of tests (ornithine
in one instance and insulin in another) was used in 12.7% of patients. The reliability of
the GH peak measured by comparing the results of 2 tests in the same patient was poor, as
measured by intraclass correlation coefficients below 0.8. Multivariate analysis
identified several parameters positively or negatively associated with peak plasma GH:
calendar year of initiation of treatment, etiology of GHD, height SD score, bone age SD
score, puberty, weight SD score, genetic target height SD score, and the nature of the
pharmacological agent used. We believe that several of these factors (weight SD score,
genetic target height SD score, and nature of the agent) identify biases in the diagnosis
of GHD. We conclude that GHST should be performed with a very limited number of agents,
interpreted after the establishment of reference values in age-matched normal children,
and associated with other clinical and biochemical parameters for establishing the
diagnosis of GHD.
- Language of Publication
- English
- Unique Identifier
- 97358161
- MeSH Heading (Major)
- Somatotropin|*BL/*DF
- MeSH Heading
- Adolescence; Age Factors; Child; Child, Preschool; Female; Human; Male; Methods;
Registries; Reproducibility of Results; Retrospective Studies
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0021-972X
- Country of Publication
- UNITED STATES
Record 19 from database: MEDLINE
Return To The Top
- Title
- Insulin induction of ornithine decarboxylase. Importance of
mRNA secondary structure and phosphorylation of eucaryotic initiation factors eIF-4B and
eIF-4E.
- Author
- Manzella JM; Rychlik W; Rhoads RE; Hershey JW; Blackshear PJ
- Address
- Howard Hughes Medical Institute Laboratories, Duke University Medical Center, Durham,
North Carolina 27710.
- Source
- J Biol Chem, 1991 Feb 5, 266:4, 2383-9
- Abstract
- We investigated the possibility that insulin could stimulate translation of ornithine decarboxylase (ODC) mRNA in a murine fibroblast cell line
that expresses large numbers of human insulin receptors (HIR 3.5 cells). Within 3 h after
exposure to 70 nM insulin, ODC enzyme activity increased approximately 50-fold and mRNA
accumulation 3-fold in the HIR 3.5 cells but not in normal fibroblasts. Pretreatment of
cells with cycloheximide completely inhibited insulin-stimulated ODC expression;
actinomycin D partially inhibited this effect. To determine the influence of the 5'
untranslated region (5'UTR) of ODC mRNA on insulin-regulated ODC expression, plasmids were
constructed which contained sequences from the 5'UTR of a rat ODC mRNA interposed between
the ferritin promoter and the coding region of the human growth hormone gene. These
constructions were then expressed transiently in HIR 3.5 cells. Insulin stimulated a
2-4-fold change in growth hormone accumulation in the medium of cells transiently
expressing plasmids containing the entire 5'UTR of ODC mRNA or just the 5'-most 115 bases,
a G/C-rich conserved sequence predicted to form a stem-loop structure and shown previously
to be responsible for constitutive inhibition of translation. There was a direct
correlation between the extent of insulin stimulation and the predicted secondary
structure of the added 5'UTR sequences. To determine whether this effect might be due to
insulin activation of initiation factors responsible for melting mRNA secondary structure,
we examined the effect of insulin on the phosphorylation states of two such factors,
eucaryotic initiation factors eIF-4B and eIF-4E. Insulin stimulated the phosphorylation of
both initiation factors; this stimulation was evident at 15 min and maximal by 60 min.
These results suggest a potential general mechanism by which insulin could preferentially
stimulate translation of mRNAs whose 5'UTRs exhibit significant secondary structure by
activating initiation factors involved in melting such secondary structures.
- Language of Publication
- English
- Unique Identifier
- 91115858
- MeSH Heading (Major)
- Insulin|*PD; Ornithine Decarboxylase|*BI/GE; Peptide Initiation Factors|*ME; RNA,
Messenger|*CH/GE
- MeSH Heading
- Animal; Blotting, Northern; Cell Line; Cloning, Molecular; Cycloheximide|PD;
Dactinomycin|PD; Dose-Response Relationship, Drug; Enzyme Induction; Human; Mice; Nucleic
Acid Conformation; Phosphorylation; Receptors, Insulin|ME; Support, Non-U.S. Gov't;
Support, U.S. Gov't, P.H.S.; Translation, Genetic
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0021-9258
- Country of Publication
- UNITED STATES
- CAS Registry/EC Number
- EC 4.1.1.17 (Ornithine Decarboxylase); 0 (eIF-4B); 0 (eIF-4E); 0 (Peptide Initiation
Factors); 0 (Receptors, Insulin); 0 (RNA, Messenger); 11061-68-0 (Insulin); 50-76-0
(Dactinomycin); 66-81-9 (Cycloheximide)
Record 20 from database: MEDLINE
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- Title
- Polyamine involvement in the growth of hormone-responsive and -resistant human breast
cancer cells in culture.
- Author
- Glikman P; Manni A; Demers L; Bartholomew M
- Address
- Department of Medicine, Milton S. Hershey Medical Center, Pennsylvania State University,
Hershey 17033.
- Source
- Cancer Res, 1989 Mar 15, 49:6, 1371-6
- Abstract
- Recent evidence indicates that hormone-responsive but not -resistant human breast cancer
cells in culture are sensitive to the antiproliferative effect of the polyamine (PA)
biosynthetic inhibitor alpha-difluoromethylornithine (DFMO).
The present experiments were designed to investigate the potential differential
involvement of the PA pathway in the growth of these different biological subtypes of
human breast cancer. Thus, we evaluated the effect of DFMO on proliferation, ornithine decarboxylase (ODC) activity, and PA levels of the
hormone-dependent MCF-7 and -independent MDA-MB-231 breast cancer cell lines. When tested
at comparable cell density, the two cell lines had similar levels of ODC activity and PA.
Administration of DFMO (0.01, 0.1, 1, 4 mM) for 6 days caused a similar dose-dependent
inhibition of proliferation (up to approximately 15% of control) associated with
suppression of ODC activity to undetectable levels at the highest dose. In both cell
lines, putrescine and spermidine levels were maximally suppressed by doses of DFMO greater
than 0.1 mM. Higher doses of DFMO (1 and 4 mM) also suppressed spermine levels to
approximately 60% of control. In detailed time-course studies, DFMO administration (0.1
mM) similarly suppressed by 80% the rise in ODC observed in both cell lines following a
medium change. At all time points, putrescine and spermidine levels were likewise
suppressed to a similar extent. Addition of putrescine (0.1-2.5 mM) to DFMO-treated cells
repleted cellular PA levels and restored growth to approximately 80% of control in both
cell lines. We conclude that, under these experimental conditions, PA are similarly
involved in the growth of the hormone-responsive MCF-7 and -resistant MDA-MB-231 human
breast cancer cell lines.
- Language of Publication
- English
- Unique Identifier
- 89168158
- MeSH Heading (Major)
- Biogenic Polyamines|*PH; Breast Neoplasms|*PA; Neoplasms, Hormone-Dependent|*PA
- MeSH Heading
- Cell Count; Dose-Response Relationship, Drug; Eflornithine|PD; Female; Human; Ornithine
Decarboxylase|AN; Putrescine|PD; Support, U.S. Gov't, P.H.S.; Time Factors; Tumor Cells,
Cultured
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0008-5472
- Country of Publication
- UNITED STATES
- CAS Registry/EC Number
- EC 4.1.1.17 (Ornithine Decarboxylase); 0 (Biogenic Polyamines); 110-60-1 (Putrescine);
70052-12-9 (Eflornithine)
Record 21 from database: MEDLINE
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- Title
- Polyamine involvement in the secretion and action of TGF-alpha in hormone sensitive
human breast cancer cells in culture.
- Author
- Kim I; Manni A; Lynch J; Demers L
- Address
- Department of Medicine, Milton S. Hershey Medical Center, Pennsylvania State University,
Hershey, PA 17033.
- Source
- Breast Cancer Res Treat, 1991 May, 18:2, 83-91
- Abstract
- These experiments were designed to test polyamine (PA) involvement in the secretion and
action of transforming growth factor alpha (TGF-alpha) in hormone responsive MCF-7 breast
cancer cells in liquid culture. At the same time, we evaluated the influence of culture
conditions (with serum vs. serum depleted) and subclonality of MCF-7 cells on PA
involvement in estrogen (E2) and TGF-alpha stimulated cell proliferation. Despite inducing
a profound suppression of cellular PA levels and inhibiting basal and E2-stimulated
growth, administration of the PA synthesis inhibitor alpha-difluoromethylornithine (DFMO) did not influence either basal or E2-induced
TGF-alpha secretion. In the same experiments, on the other hand, addition of DFMO
completely blocked the growth stimulatory effect of exogenous TGF-alpha. However, when the
culture conditions were changed to serum-free medium, TGF-alpha and E2-induced cell
proliferation was affected modestly or not at all by DFMO administration, despite similar
suppression of cellular ornithine decarboxylase (ODC)
activity and PA levels. In addition, different clones of MCF-7 cells differed in their
sensitivity to the antiproliferative effect of DFMO as well as in basal levels of ODC
activity and PA. We conclude that PAs are not involved in basal or E2-stimulated TGF-alpha
secretion in MCF-7 breast cancer cells. On the other hand, PAs do seem to be important
mediators of TGF-alpha and E2-induced breast cancer cell proliferation, though the degree
of such involvement appears to be influenced by serum factors and clonal variability of
MCF-7 cells.
- Language of Publication
- English
- Unique Identifier
- 92004007
- MeSH Heading (Major)
- Breast Neoplasms|*ME/PA; Polyamines|*PD; Transforming Growth Factor alpha|*SE
- MeSH Heading
- Cell Division|DE; Eflornithine|PD; Estrogens|PH; Human; In Vitro; Neoplasms,
Hormone-Dependent; Putrescine|PD/PH; Serum Albumin, Bovine|PD; Spermidine|PH; Spermine|PH;
Support, U.S. Gov't, P.H.S.; Tumor Cells, Cultured
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0167-6806
- Country of Publication
- NETHERLANDS
- CAS Registry/EC Number
- 0 (Estrogens); 0 (Polyamines); 0 (Serum Albumin, Bovine); 0 (Transforming Growth Factor
alpha); 110-60-1 (Putrescine); 124-20-9 (Spermidine); 70052-12-9 (Eflornithine); 71-44-3
(Spermine)
Record 22 from database: MEDLINE
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- Title
- Failure of commercial oral amino acid supplements to increase serum growth hormone
concentrations in male body-builders.
- Author
- Lambert MI; Hefer JA; Millar RP; Macfarlane PW
- Address
- Dept. of Physiology, University of Cape Town Medical School, South Africa.
- Source
- Int J Sport Nutr, 1993 Sep, 3:3, 298-305
- Abstract
- Amino acids are commonly ingested as ergogenic acids in the belief that they enhance
protein synthesis and stimulate growth hormone release. The aim of this study was to
determine the acute effect that amino acid supplements have on serum growth hormone (GH)
concentration. Seven male body-builders reported to the laboratory on four occasions after
an 8-hr fast and ingested, in random order, either a placebo, a 2.4-g arginine/lysine
supplement, a 1.85-g ornithine/tyrosine supplement, or a 20-g
BovrilR drink. Blood was collected before each treatment and again every 30 minutes for 3
hours for the measurement of serum GH concentration. On a separate occasion, subjects had
an intravenous infusion of 0.5 microgram GH-releasing hormone.kg-1 body weight to confirm
that GH secretory response was normal. The main finding was that serum GH concentrations
were not altered consistently in healthy young males following the ingestion of the amino
acid supplements in the quantities recommended by the manufacturers.
- Language of Publication
- English
- Unique Identifier
- 94035086
- MeSH Heading (Major)
- Amino Acids|AD/*PD; Somatotropin|AD/BL/*DE; Weight Lifting|*PH
- MeSH Heading
- Administration, Oral; Adult; Human; Male; Support, Non-U.S. Gov't
- Publication Type
- CLINICAL TRIAL; JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL
- ISSN
- 1050-1606
- Country of Publication
- UNITED STATES
- CAS Registry/EC Number
- 0 (Amino Acids); 9002-72-6 (Somatotropin)
Record 23 from database: MEDLINE
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- Title
- Cellular and molecular basis of intestinal and pancreatic adaptation.
- Author
- Dowling RH
- Address
- Gastroenterology Unit, Guy's Hospital, London, U.K.
- Source
- Scand J Gastroenterol Suppl, 1992, 193:, 64-7
- Abstract
- This article reviews the structural and functional changes which develop in the
intestine and pancreas in response to a variety of stimuli and which characterise adaptive
hyper- or hypo-plasia. It then discusses the principal physiological mechanisms
controlling this adaptive growth. In the gut, these include luminal nutrition, endocrine,
autocrine and paracrine hormonal influences, growth factors, enterotrophic components of
pancreatico-biliary secretions, neural factors, changes in blood flow and
mesenchyme-epithelial interactions. The cell biology of adaptive growth involves cell
membrane receptors (first messengers) and a cascade of intracellular second messengers,
the best studied of which is changes in polyamine metabolism and in related enzymes. The
effects of ornithine decarboxylase (ODC) blockade with
difluoromethyl ornithine (DFMO) and of diamine oxidase (DAO)
blockade with aminoguanidine, are described. In general, DFMO inhibits or prevents
adaptive hyperplasia while in the small bowel, aminoguanidine treatment induces
'supranormal' adaptation. However, both the gut and the pancreas transport 'exogenous'
(ingested in food and circulating in the blood stream) polyamines across their apical and
basolateral membranes. The influence of this exogenous polyamine transport on 'endogenous'
(enzyme-regulated) intracellular polyamine concentrations, is largely unknown. Finally,
the molecular biology of adaptive growth is described briefly--as illustrated by the use
of a growth hormone transgenic model in which mice develop marked intestinal mucosal
hyperplasia and increases in the relative abundance of insulin-like growth factor-I
(IGF-I) mRNA in the intestine.
- Language of Publication
- English
- Unique Identifier
- 93174201
- MeSH Heading (Major)
- Adaptation, Physiological|*; Intestines|ME/PA/*PH; Pancreas|ME/PA/*PH
- MeSH Heading
- Amine Oxidase (Copper-Containing)|ME; Animal; Cell Division; Human; Hyperplasia;
Polyamines|ME; RNA, Messenger
- Publication Type
- JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL
- ISSN
- 0085-5928
- Country of Publication
- NORWAY
- CAS Registry/EC Number
- EC 1.4.3.6 (Amine Oxidase (Copper-Containing)); 0 (Polyamines); 0 (RNA, Messenger)
Record 24 from database: MEDLINE
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- Title
- Effects of parathyroid hormone on ornithine decarboxylase
activity in human osteosarcoma cells.
- Author
- Goto H; Matsui-Yuasa I; Otani S; Morisawa S; Nishizawa Y; Morii H
- Address
- Department of Biochemistry, Osaka City University Medical School, Japan.
- Source
- Arch Biochem Biophys, 1991 May 1, 286:2, 316-22
- Abstract
- Ornithine decarboxylase (ODC) is a rate-limiting enzyme of
the biosynthesis of polyamines, which are important in cell growth and differentiation.
Here, we studied whether parathyroid hormone (PTH) affects the induction of ODC and the
proliferation of the human osteoblast-like cell line SaOS2, which is sensitive to PTH. In
confluent cells, ODC activity was not detected, but activity was significantly induced by
fresh medium, with maximum activity 6 h after the change. PTH potentiated this enzyme
induction in a dose-dependent manner at 10(-9) and 10(-8) M at which range the
intracellular cAMP level also rose. Dibutyryl cAMP, cholera toxin, and
3-isobutyl-1-methylxanthine each caused an increase in ODC activity similar to that with
PTH. The half-life of enzyme activity was about 30 min and was not changed by the addition
of PTH. mRNA coding for ODC was detected in the confluent cells and its concentration was
increased two- to threefold by the fresh medium. No further increase in mRNA occurred when
PTH was added. At 48 h after the change of medium, PTH inhibited the DNA synthesis induced
by fresh medium. These results suggest that the increase in ODC activity caused by PTH was
caused by enhancement of cAMP synthesis, and that this augmentation involves
post-transcriptional regulation.
- Language of Publication
- English
- Unique Identifier
- 91378318
- MeSH Heading (Major)
- Cyclic AMP|*ME; Ornithine Decarboxylase|*ME; Parathyroid Hormones|*PD; Peptide
Fragments|*PD
- MeSH Heading
- Bucladesine|PD; Butyric Acids|PD; Cell Line; DNA Replication|DE; Eflornithine|PD; Human;
Kinetics; Nucleic Acid Hybridization; Osteosarcoma; Polyamines|ME; RNA, Neoplasm|GE/IP
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0003-9861
- Country of Publication
- UNITED STATES
- CAS Registry/EC Number
- EC 4.1.1.17 (Ornithine Decarboxylase); 0 (Butyric Acids); 0 (Parathyroid Hormones); 0
(Peptide Fragments); 0 (Polyamines); 0 (RNA, Neoplasm); 107-92-6 (butyric acid); 362-74-3
(Bucladesine); 52232-67-4 (Teriparatide); 60-92-4 (Cyclic AMP); 70052-12-9 (Eflornithine)
Record 25 from database: MEDLINE
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- Title
- Variations in amplification and expression of the ornithine
decarboxylase gene in human breast cancer cells.
- Author
- Thomas T; Kiang DT; Jänne OA; Thomas TJ
- Address
- Department of Environmental and Community Medicine, UMDNJ-Robert Wood Johnson Medical
School, Piscataway 08854.
- Source
- Breast Cancer Res Treat, 1991 Nov, 19:3, 257-67
- Abstract
- The polyamine biosynthetic pathway plays a critical role in the growth of human breast
cancer cells. Ornithine decarboxylase (ODC) is a key enzyme
in polyamine biosynthesis. To understand the regulation of ODC activity and polyamine
accumulation in breast cancer cells, we studied amplification and expression of the ODC
gene in four breast cancer cell lines. ODC gene dosage was analyzed by Southern blot
hybridization and was 4- to 12-fold higher in T-47D, MDA-MB-231, and BT-20 cell lines than
in the MCF-7 cell line. ODC mRNA level was 2- to 3-fold higher in BT-20 and MDA-MB-231
cell lines than in the other two lines. We also measured ODC activity and polyamine
concentration in these cell lines, and determined their sensitivity to an ODC inhibitor,
difluoromethylornithine (DFMO). BT-20 cells showed
significantly higher ODC activity and polyamine concentrations than the other three cell
lines. BT-20 cells were resistant to the growth inhibitory effect of DFMO even at 4 mM
concentration, whereas the proliferation of MCF-7, T47D, and MDA-MB-231 cells was
inhibited by this drug. These results suggest that different transcriptional and
post-transcriptional mechanisms control the regulation of ODC gene expression in breast
cancer cell lines.
- Language of Publication
- English
- Unique Identifier
- 92135858
- MeSH Heading (Major)
- Adenocarcinoma|EN/*PA; Breast Neoplasms|EN/*PA; Carcinoma|EN/*PA; Carcinoma,
Intraductal, Noninfiltrating|EN/*PA; Neoplasm Proteins|BI/*GE; Ornithine
Decarboxylase|BI/*GE
- MeSH Heading
- Comparative Study; DNA, Neoplasm|GE; Eflornithine|PD; Enzyme Induction; Estrogens;
Female; Gene Amplification; Gene Expression Regulation, Neoplastic; Human; Neoplasms,
Hormone-Dependent|EN/PA; Polyamines|AN; RNA, Messenger|BI; RNA, Neoplasm|AN; Support, U.S.
Gov't, P.H.S.; Tumor Cells, Cultured|DE/EN
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0167-6806
- Country of Publication
- NETHERLANDS
- CAS Registry/EC Number
- EC 4.1.1.17 (Ornithine Decarboxylase); 0 (DNA, Neoplasm); 0 (Estrogens); 0 (Neoplasm
Proteins); 0 (Polyamines); 0 (RNA, Messenger); 0 (RNA, Neoplasm); 70052-12-9
(Eflornithine)
Record 26 from database: MEDLINE
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- Title
- Comparison of growth hormone response to growth hormone-releasing factor 1-44 according
to the combined study of sleep secretion with the responses to pharmacologic stimuli.
- Author
- Garnier P; Liapi C; Raynaud F; Evain-Brion D
- Address
- Fondation de Recherche en Hormonologie, Fresnes, France.
- Source
- Horm Res, 1987, 28:1, 13-9
- Abstract
- The growth hormone (GH) response to GH-releasing factor (GRF) was studied in 54 severely
growth-retarded patients (-2.1 to -6.5 SD) aged from 5 to 20 years (32 males and 22
females), among whom 34 were prepubertal and 20 at early pubertal stages. The patients
were also submitted to a standard evaluation of their GH secretion, consisting of at least
two classical pharmacologic stimulation (CPS) tests, such as ornithine,
arginine and/or insulin, and one study of the GH sleep secretion (SS). The results of the
standard evaluation allowed to distinguish 5 groups: (I) endocrinologically normal (n =
26); (II) completely GH deficient (n = 5); (III) partially GH deficient (n = 8); (IV)
dissociated GH secretions with normal SS (n = 9), and (V) dissociated GH secretions with
low SS (n = 6). The GH responses to GRF were correlated with both responses to CPS and SS.
There was a large overlap of the individual responses to GRF between the 5 groups, but the
mean responses in groups II, IV and V were significantly lower than in group I.
Furthermore, the mean responses of groups IV and V were in the lower range of the normal.
It is concluded that the GRF test may be useful to ascertain the diagnosis of functional
or partial GH deficiency when the responses to CPS and SS are dissociated.
- Language of Publication
- English
- Unique Identifier
- 88197053
- MeSH Heading (Major)
- Growth Disorders|*ME; Sleep|*PH; Somatotropin|DF/*SE; Somatotropin-Releasing Hormone|*DU
- MeSH Heading
- Adolescence; Adult; Child; Child, Preschool; Comparative Study; Female; Human; Male;
Pituitary Function Tests|MT; Pituitary Gland|DE/SE
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0301-0163
- Country of Publication
- SWITZERLAND
- CAS Registry/EC Number
- 9002-72-6 (Somatotropin); 9034-39-3 (Somatotropin-Releasing Hormone)
Record 27 from database: MEDLINE
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- Title
- Statistical study of 5473 results of nine pharmacological stimulation tests: a proposed
weighting index.
- Author
- Rochiccioli P; Enjaume C; Tauber MT; Pienkowski C
- Address
- Service de Pédiatrie, CHU Purpan, Toulouse, France.
- Source
- Acta Paediatr, 1993 Mar, 82:3, 245-8
- Abstract
- A total of 5473 pharmacological stimulation tests were carried out in 3143 children and
subjected to statistical analysis. The mean chronological age of the children was 9 years
9 months (range 3 years to 16 years 6 months) and mean bone age was 7 years 6 months
(range 2 years to 14 years). Nine pharmacological tests were used: (1) arginine (n = 625);
(2) clonidine (n = 339); (3) insulin (n = 198); (4) ornithine
(n = 162); (5) insulin and arginine (n = 203); (6) clonidine and betaxolol (n = 2003); (7)
L-dopa (n = 685); (8) glucagon and propranolol (n = 443); and (9) glucagon and betaxolol
(n = 815). Measurement of plasma growth hormone was always performed using the same
method. The distribution of values in each test was of the gausso-logarithmic type. The
results of the mean peak and the 95% confidence limit were as follows: (1) 10.2, 0.45; (2)
11.5, 0.7; (3) 11.8, 0.8; (4) 14.2, 1.2; (5) 14.3, 0.9; (6) 15.7, 1.1; (7) 19.8, 2.1; (8)
20.8, 2.3; (9) 21, 2.5. These results lead to the following conclusions: the specificity
of these tests is low, the mean peak may vary two-fold from one test to another, and the
percentage of peaks < 10 ng/ml ranges from 69% for test 1 to 29% for tests 8 and 9. The
proportion of growth hormone deficiencies thus varies considerably according to the test
used.(ABSTRACT TRUNCATED AT 250 WORDS)
- Language of Publication
- English
- Unique Identifier
- 93264725
- MeSH Heading (Major)
- Drugs|*DU; Growth Disorders|BL/*DI
- MeSH Heading
- Adolescence; Child; Child, Preschool; Comparative Study; Female; Human; Male;
Retrospective Studies; Sensitivity and Specificity; Somatotropin|BL/DF
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0803-5253
- Country of Publication
- NORWAY
- CAS Registry/EC Number
- 0 (Drugs); 9002-72-6 (Somatotropin)
Record 28 from database: MEDLINE
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- Title
- Human promyelocytic cell line HL60 has the specific binding sites for prolactin and its ornithine decarboxylase, DNA synthesis and cellular proliferation
are induced by prolactin.
- Author
- Nishiguchi Y; Hibasami H; Komada Y; Sakurai M; Nakashima K
- Address
- Department of Biochemistry, Mie University Faculty of Medicine, Japan.
- Source
- Leuk Res, 1993 Aug, 17:8, 633-7
- Abstract
- Human prolactin (hPRL) induced ornithine decarboxylase
(ODC) activity, subsequently DNA synthesis and cellular proliferation on human
promyelocytic cells, HL60, cultured in a serum-free medium. HL60 cells had 2100 specific
binding sites for hPRL per cell, showing a dissociation constant of 1.1 x 10(-10) M.
Binding of 125I-PRL to the cells was not blocked by simultaneous addition of human growth
hormone. ODC activity and DNA synthesis were activated maximally at 5 and 20 h,
respectively, after the addition of 0.05 nM hPRL. These effects of PRL on cellular
proliferation, ODC activity and DNA synthesis were abolished by the simultaneous addition
of anti-hPRL antibody. Simultaneous addition of an irreversible inhibitor of ODC,
difluoromethyl ornithine (DFMO), also abolished the
inductions of ODC and DNA synthesis by hPRL. The inhibitory effect of DFMO on hPRL-induced
DNA synthesis was reversed by the addition of putrescine to the culture medium. These
results suggest that hPRL binds to the prolactin receptor on HL60 cells and induces ODC
activity to increase cellular polyamine levels, which eventually stimulates DNA synthesis
and cellular proliferation.
- Language of Publication
- English
- Unique Identifier
- 93360545
- MeSH Heading (Major)
- Cell Division|*DE; DNA Replication|*DE; Leukemia, Promyelocytic, Acute|*ME/PA; Ornithine
Decarboxylase|*BI; Prolactin|ME/*PD; Receptors, Prolactin|*BI
- MeSH Heading
- Binding Sites; Carbon Radioisotopes; Dose-Response Relationship, Drug; DNA, Neoplasm|BI;
Enzyme Induction; Human; Iodine Radioisotopes; Kinetics; Thymidine|ME; Tritium; Tumor
Cells, Cultured
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0145-2126
- Country of Publication
- ENGLAND
- CAS Registry/EC Number
- EC 4.1.1.17 (Ornithine Decarboxylase); 0 (Carbon Radioisotopes); 0 (DNA, Neoplasm); 0
(Iodine Radioisotopes); 0 (Receptors, Prolactin); 10028-17-8 (Tritium); 50-89-5
(Thymidine); 9002-62-4 (Prolactin)
Record 29 from database: MEDLINE
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- Title
- Retinoic acid regulates ornithine decarboxylase gene
expression at the transcriptional level.
- Author
- Mao Y; Gurr JA; Hickok NJ
- Address
- Department of Dermatology, Jefferson Institute of Molecular Medicine, Thomas Jefferson
University, Philadelphia, PA 19107.
- Source
- Biochem J, 1993 Nov 1, 295 ( Pt 3):, 641-4
- Abstract
- Retinoic acid (RA) is important for normal mammalian development and growth. Ornithine decarboxylase (ODC) is the first and rate-limiting enzyme
in the biosynthesis of the polyamines, and we have previously shown that ODC mRNA levels
are suppressed by RA in human skin cells. Using HeLa cells, we now show that treatment
with 0.5 microM RA for 24 h suppresses endogenous ODC mRNA levels and the expression of a
transfected ODC/chloramphenicol acetyltransferase plasmid (Kpn-ODCCAT), containing
sequences from -1450 to +810 of the human ODC gene. Co-transfection with either the
alpha-RA receptor (alpha-RAR) or a chimeric alpha-RA/oestrogen receptor (alpha-RAER)
followed by treatment with the cognate hormone suppresses expression of Kpn-ODCCAT and
Not-ODCCAT, which contains sequences from -250 to +514. Liganded alpha-RAR suppresses the
activity of Kpn-ODCCAT more markedly than does liganded alpha-RAER (98% and 80%
suppression, respectively), whereas both receptors have very similar effects on Not-ODCCAT
expression (73% and 67% suppression, respectively). The unliganded alpha-RAR suppresses
Kpn-ODCCAT by 76%, whereas unliganded alpha-RAER has no significant effect. These data
show that RA regulates ODC-gene expression at the transcriptional level, and that
alpha-RAR, but not alpha-RAER, can confer full hormonal responsiveness. This suggests that
the activating function present in the alpha-RAR ligand-binding domain is required for
full transcriptional regulation.
- Language of Publication
- English
- Unique Identifier
- 94059011
- MeSH Heading (Major)
- Gene Expression Regulation|*DE; Ornithine Decarboxylase|*GE; Transcription, Genetic|*DE;
Tretinoin|*PD
- MeSH Heading
- Animal; Blotting, Northern; Cell Line; Cercopithecus aethiops; Hela Cells; Human;
Kidney; Receptors, Estrogen|GE/PH; Receptors, Retinoic Acid|GE/PH; RNA, Messenger|ME;
Support, U.S. Gov't, P.H.S.; Transfection
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0264-6021
- Country of Publication
- ENGLAND
- CAS Registry/EC Number
- EC 4.1.1.17 (Ornithine Decarboxylase); 0 (Receptors, Estrogen); 0 (Receptors, Retinoic
Acid); 0 (RNA, Messenger); 302-79-4 (Tretinoin)
Record 30 from database: MEDLINE
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- Title
- Low-dose amino acid supplementation: no effects on serum human growth hormone and
insulin in male weightlifters.
- Author
- Fogelholm GM; Näveri HK; Kiilavuori KT; Härkönen MH
- Address
- Dept. of Applied Chemistry and Microbiology, University of Helsinki, Finland.
- Source
- Int J Sport Nutr, 1993 Sep, 3:3, 290-7
- Abstract
- Using a double-blind, crossover protocol, we studied the possible effects of a 4-day
combined L-arginine, L-ornithine, and L-lysine
supplementation (each 2 g/day, divided into two daily doses) on 24-hr level of serum human
growth hormone (hGH) and insulin in 11 competitive weightlifters, ages 19 to 35 yrs. Three
similar daily hGH peaks, seemingly preceded by a decrease in serum insulin concentration,
were found during both amino acid and placebo supplementation. Supplementation did not
affect the physiological variation of serum hGH concentration (treatment and treatment x
time interaction: p = 0.43-0.55). Analogously, serum insulin levels were not higher after
amino acid supplementation. Therefore the ergogenic value of low-dose oral amino acid
supplementation in increasing hGH or insulin secretion seems questionable.
- Language of Publication
- English
- Unique Identifier
- 94035085
- MeSH Heading (Major)
- Amino Acids|AD/*PD; Somatotropin|BL/*DE; Weight Lifting|*PH
- MeSH Heading
- Adult; Double-Blind Method; Drug Administration Schedule; Human; Insulin|ME; Male;
Support, Non-U.S. Gov't
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 1050-1606
- Country of Publication
- UNITED STATES
- CAS Registry/EC Number
- 0 (Amino Acids); 11061-68-0 (Insulin); 9002-72-6 (Somatotropin)
Record 31 from database: MEDLINE
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- Title
- Analogues of luteinizing hormone-releasing hormone containing cytotoxic groups.
- Author
- Janáky T; Juhász A; Bajusz S; Csernus V; Srkalovic G; Bokser L; Milovanovic S; Redding
TW; Rékási Z; Nagy A; et al
- Address
- Endocrine, Polypeptide and Cancer Institute, Veterans Affairs Medical Center, New
Orleans, LA.
- Source
- Proc Natl Acad Sci U S A, 1992 Feb 1, 89:3, 972-6
- Abstract
- In an attempt to produce better cytotoxic analogues, chemotherapeutic antineoplastic
radicals including an alkylating nitrogen mustard derivative of D-phenylalanine
(D-melphalan), reactive cyclopropane, anthraquinone derivatives
[2-(hydroxymethyl)anthraquinone and the anticancer antibiotic doxorubicin], and an
antimetabolite (methotrexate) were coupled to suitably modified agonists and antagonists
of luteinizing hormone-releasing hormone (LH-RH). Analogues with D-lysine6 and D-ornithine6 or N epsilon-(2,3-diaminopropionyl)-D-lysine and N
delta-(2,3-diaminopropionyl)-D-ornithine were used as
carriers for one or two cytotoxic moieties. The enhanced biological activities produced by
the incorporation of D amino acids into position 6 of the agonistic analogues were further
increased by the attachment of hydrophobic cytotoxic groups, resulting in compounds with
10-50 times higher activity than LH-RH. Most of the monosubstituted agonistic analogues
showed high affinities for the membrane receptors of human breast cancer cells, while the
receptor binding affinities of peptides containing two cytotoxic side chains were lower.
Antagonistic carriers [Ac-D-Nal(2)1,D-Phe(4Cl)2,D-Trp3, Arg5,D-Lys6,D-Ala10] LH-RH [where
Nal(2) is 3-(2-naphthyl)alanine], [Ac-D-Nal(2)1,D-Phe(4Cl)2,D-Trp3,Arg5,N
epsilon-(2,3-diaminopropionyl)-D-Lys6,D- Ala10]LH-RH, and their D-Pal(3)3 homologs [Pal(3)
is 3-(3-pyridyl)alanine] as well as [Ac-D-Nal(2)1,D-Phe(4Cl)2,D-Pal(3)3,Tyr5,N
epsilon-(2,3-diamino-propionyl)-D-Lys6,D-Ala10]LH-RH were linked to cytotoxic compounds.
The hybrid molecules inhibited ovulation in rats at doses of 10 micrograms and suppressed
LH release in vitro. The receptor binding of cytotoxic analogues was decreased compared to
the precursor peptides, although analogues with 2-(hydroxymethyl)anthraquinone
hemiglutarate had high affinities. All of the cytotoxic analogues tested inhibited
[3H]thymidine incorporation into DNA in cultures of human breast and prostate cancer cell
lines. Some cytotoxic analogues also significantly suppressed the growth of mammary and
prostate cancers in vivo in animal models.
- Language of Publication
- English
- Unique Identifier
- 92141240
- MeSH Heading (Major)
- Cytotoxins|*AD; Gonadorelin|*AA/ME; Hormones, Synthetic|*CH
- MeSH Heading
- Amino Acid Sequence; Animal; Antimetabolites, Antineoplastic|AD; Cell Division|DE;
Human; In Vitro; Molecular Sequence Data; Rats; Receptors, LHRH|ME; Structure-Activity
Relationship; Support, U.S. Gov't, Non-P.H.S.; Support, U.S. Gov't, P.H.S.; Tumor Cells,
Cultured
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0027-8424
- Country of Publication
- UNITED STATES
- CAS Registry/EC Number
- 0 (Antimetabolites, Antineoplastic); 0 (Cytotoxins); 0 (Hormones, Synthetic); 0
(Receptors, LHRH); 33515-09-2 (Gonadorelin)
Record 32 from database: MEDLINE
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- Title
- Role of gastrin as a trophic hormone.
- Author
- Walsh JH
- Address
- Center for Ulcer Research and Education, Wadsworth Veterans Administration Center, Los
Angeles, Calif.
- Source
- Digestion, 1990, 47 Suppl 1:, 11-6; discussion 49-52
- Abstract
- Gastrin has two principal biological effects: stimulation of acid secretion from gastric
parietal cells and stimulation of mucosal growth in the acid-secreting part of the
stomach. Circulating gastrin regulates the increase in acid secretion that occurs during
the after meals. Gastrin also stimulates mucosal growth in the stomach. Exogenously
administered gastrin causes increased cell division in the proliferative zone that lies
between the surface cells and the gastric glands in the acid-secreting mucosa. The newly
formed cells undergo differentiation into surface epithelial cells, parietal cells and
gastric enterochromaffin-like cells. Furthermore, the increased mucosal proliferation that
occurs with refeeding after a period of fasting may be mediated by gastrin since refeeding
stimulates gastrin production and a parallel increase in mucosal DNA synthesis. Both food
and gastrin cause a rapid increase in cell division and an increase in gastric ornithine decarboxylase mRNA in fasting rats. In preliminary
immunoneutralization experiments, the stimulation of ornithine
decarboxylase produced by food was inhibited by gastrin antibody. The sustained inhibition
of gastric acid secretion obtained by surgery or with antisecretory drug therapy results
in hypergastrinaemia associated with increased gastric mucosal cell proliferation. A good
correlation between gastric enterochromaffin-like cell density and circulating gastrin
concentrations has been found under these conditions as well as during infusions of
exogenous gastrin. Trophic effects of gastrin have also been reported for the colon,
duodenum and pancreas, but chronic hypergastrinaemia does not appear to produce
hyperplasia of these organs.(ABSTRACT TRUNCATED AT 250 WORDS)
- Language of Publication
- English
- Unique Identifier
- 91231139
- MeSH Heading (Major)
- Gastric Acid|*SE; Gastrins|PD/*PH; Parietal Cells, Gastric|*SE
- MeSH Heading
- Animal; Cell Division|DE; Gastric Mucosa|CY/DE; Human; Omeprazole|PD
- Publication Type